ERAS Comes of Age With Opioid-Free Breast Cancer Surgery

In In The News by Barbara Jacoby

From: clinicaloncology.com

Full commitment to the enhanced recovery after surgery (ERAS) protocol at Maimonides Medical Center, in New York City, eliminated the use of opioids in more than 1,200 patients undergoing breast-conserving surgery. Furthermore, patients managed with ERAS reported less pain than usual-care patients receiving opioids, according to the medical center’s chairman of surgery, Patrick Borgen, MD, who described the opioid-sparing approach at the 2020 Miami Breast Cancer Conference.

The ERAS protocol uses ketorolac, acetaminophen, gabapentin and local injections as substitutes for opioids and, by all measures, is equally effective for postoperative pain. Dr. Borgen added that the opioid-sparing approach he helped develop is addressing the crisis of opioid addiction, noting that the vast majority of people addicted to heroin are introduced to narcotics by a prescription from a physician.

Individuals who are opioid-naive at surgery have the highest risk for chronic opioid use, and up to 10% of patients treated with opioids postoperatively will continue to use them. The likelihood of dependence after surgery is linearly related to the number of days for which opioids were prescribed, Dr. Borgen said.

High Risk for Opioid Abuse After Mastectomy

Reducing opioids can have positive outcomes for oncology patients. Undergoing mastectomy puts patients at three times the risk for also experiencing opioid abuse and addiction. The other concern in this setting is opioids’ potentially detrimental effect on cancer prognosis, Dr. Borgen said. Opioids impair the immune response, increase angiogenesis, change natural killer cells and T-cell function, and may act directly on tumor cells to promote growth and metastasis.

However, opioids can’t just be cut out of the equation, he said. “This is not just about eliminating opioids and allowing pain. We’ve got to control pain while eliminating opioids.”

The first step in approaching this form of pain control after breast cancer surgery is to set expectations for the patient, assuring that pain will be controlled and she will not require opioids at discharge. “Setting expectations is one-third of the battle,” Dr. Borgen said.

Opioid-Minimizing ERAS Protocol At Maimonides

Patients are allowed to have clear liquids up to two hours preoperatively. In the preoperative holding area, they receive oral acetaminophen (975 mg) and gabapentin (300 mg). The use of a low dose of gabapentin is based on a systematic review of placebo-controlled trials showing that 300 mg given preoperatively significantly reduced the need for opioids (J Pain Res 2016;9:631-640).

Intraoperatively, normothermia is an important concern. Dr. Borgen’s team uses a blanket patient warming system prior to anesthesia. Maintenance of euvolemia, initiation of an antiemetic protocol upon induction, and use of long-acting local anesthesia and a 1.5-mg IV dose of ketorolac at incision closure also are part of the protocol.

For long-acting analgesia, the team uses 1.3% liposomal bupivacaine (Exparel, Pacira BioSciences) diluted 1:1 with 0.5% bupivacaine without epinephrine, and to achieve a larger volume for injection, they dilute the liposomal bupivacaine 1:4 with 0.25% bupivacaine.

“It’s important never to mix liposomal bupivacaine with lidocaine. You will precipitate the liposomes and can wind up with a massive dose of bupivacaine,” Dr. Borgen cautioned.

“Achieving local anesthesia for up to 72 hours gets patients through that period where they used to take the most narcotics,” he said.

Liposomal Bupivacaine: Cost Considerations

“It’s very clear that the cost of liposomal bupivacaine is an issue. A 20-mL vial is approximately $300,” Dr. Borgen acknowledged. “But some progress has been made on the reimbursement front.”

The Centers for Medicare & Medicaid Services updated regulations for ambulatory surgery centers using liposomal bupivacaine in October 2019, which state:

  • Liposomal bupivacaine can be billed separately using the HCPCS code C9290. The new rule changes the payment status from “packaged” to “allowed” in ambulatory surgery centers, allowing for separate reimbursement.
  • Reimbursement is priced at $1.25 per milligram: the 20-cc vial is 266 mg and the 10-cc vial is 133 mg; the respective costs of these are approximately $325 and $175, reimbursed by Medicare at $332 and $166.

“I think this story will continue to evolve,” Dr. Borgen added.

Safety and Efficacy of Ketorolac

Concerns that ketorolac may not be a safe adjunct for postoperative pain management were dispelled in a meta-analysis of 27 studies that found no increase in perioperative bleeding (Plast Reconstr Surg 2014;133[3]:741-755). More recently, in their own single-center study, Dr. Borgen and his team also observed no increased bleeding risk with ketorolac (Ann Surg Oncol 2019;26[10]:3368-3373).

Their study compared the ERAS protocol (used by early adopters at Maimonides) with usual care. ERAS-managed patients received ketorolac, acetaminophen, gabapentin and liposomal bupivacaine, and this cocktail provided pain relief that was equivalent to opioids. Discharge oral morphine milligram equivalents (OMEs) totaled 54.5 per patient in the usual care group, versus 0 in the ERAS group (P<0.001) (Br Cancer Res Treat 2018;171[3]:621-626).

“There were no differences in pain scores at all—for the early post-op period, middle post-op, late post-op, and at 10 days, two weeks, three weeks later—for patients who received opioids versus those treated on an ERAS protocol,” Dr. Borgen reported.

The investigators then extended the breast surgery–specific ERAS protocol to mastectomy in a pilot study of 57 patients (Am J Surg 2019;218[4]:700-705). Mean OMEs at discharge were 2.4 for the ERAS group and 59.8 for the usual-care group, “an enormous difference,” Dr. Borgen noted, adding that “in this case, we actually showed that the pain scores were better in the ERAS group than in the opioid group.”

Far-Reaching Effect

Between July 2015 and June 2016, more than 63,500 OMEs were prescribed, for a mean of 202 per patient. After universal implementation of the ERAS protocol a year later, the mean number of OMEs per patient was less than 0.5 and the median number was 0. Without opioids, the average pain scores were also significantly lower in lumpectomy patients for both the first postoperative day (1.7 vs. 3.1; P<0.0001) and the week after (1.1 vs. 2.0; P<0.001).

“In our first year, at one hospital in Brooklyn, we prescribed 30,000 fewer oral MMEs. That’s enough opioids to kill 600 opioid-naive patients,” Dr. Borgen said. “Imagine what we could do if 10% or 20% of American breast surgeons adopted an ERAS protocol.”

—Clinical Oncology News Staff